英国生物库中循环生物标志物与卵巢癌风险的前瞻性分析。
Prospective Analysis of Circulating Biomarkers and Ovarian Cancer Risk in the UK Biobank.
机构信息
Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.
出版信息
Cancer Epidemiol Biomarkers Prev. 2024 Oct 2;33(10):1347-1355. doi: 10.1158/1055-9965.EPI-24-0319.
BACKGROUND
Risk factors have a limited ability to predict individuals at high risk of developing ovarian cancer among average-risk women, highlighting the need for discovery of novel biomarkers. In the UK Biobank, we investigated serum biomarkers commonly measured in clinical laboratory tests and ovarian cancer risk.
METHODS
We conducted a prospective analysis of 20 serum biomarkers and ovarian cancer risk in 232,037 female UK Biobank participants (including 1,122 incident ovarian cancer cases diagnosed from 2006 to 2020). Multivariable adjusted Cox proportional hazards models were used to examine associations between biomarkers and ovarian cancer risk overall and by histotype. FDR was used to account for multiple testing.
RESULTS
Overall, higher levels of insulin-like growth factor (IGF)-1 [RRquartile 4 vs. 1 = 0.73; 95% confidence interval (CI), 0.60-0.87; P-trend = 0.002/FDR = 0.04], HbA1c (RRquartile 4 vs. 1 = 0.74; 95% CI, 0.62-0.89; P-trend = 0.002/FDR = 0.04), and alanine aminotransferase (RRquartile 4 vs. 1 = 0.76; 95% CI, 0.63-0.91; P-trend = 0.002/FDR = 0.04) were significantly associated with lower ovarian cancer risk. When stratified by histotype, higher IGF1 levels were associated with lower risk of serous (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.58-0.91; P-trend = 0.01/FDR = 0.20) and clear cell tumors (RRquartile 4 vs. 1 = 0.18; 95% CI, 0.07-0.49; P-trend = 0.001/FDR = 0.02), and higher HbA1c levels were associated with lower risk of serous tumors (RRquartile 4 vs. 1 = 0.73; 95% CI, 0.59-0.90; P-trend = 0.004/FDR = 0.08).
CONCLUSIONS
We observed that higher levels of circulating IGF1, HbA1c, and alanine aminotransferase were associated with lower ovarian cancer risk.
IMPACT
These results suggest metabolism of glucose/amino acid and insulin/IGF1 signaling pathway may be contributing to ovarian carcinogenesis. Further research is needed to replicate our findings and elucidate how systemic changes in metabolism impact ovarian carcinogenesis.
背景
风险因素在预测普通风险女性中卵巢癌高危个体方面的能力有限，这凸显了发现新的生物标志物的必要性。在英国生物银行，我们研究了在临床实验室检测中常用的血清生物标志物与卵巢癌风险之间的关系。
方法
我们对 232037 名英国生物银行女性参与者（包括 2006 年至 2020 年期间诊断出的 1122 例卵巢癌新发病例）进行了一项前瞻性分析，研究了 20 种血清生物标志物与卵巢癌风险之间的关系。多变量调整的 Cox 比例风险模型用于总体和组织学类型上检查生物标志物与卵巢癌风险之间的关联。使用 FDR 来考虑多重检验。
结果
总体而言，较高水平的胰岛素样生长因子（IGF）-1[四分位距 4 与 1 相比=0.73；95%置信区间（CI），0.60-0.87；趋势 P 值=0.002/FDR=0.04]、糖化血红蛋白（HbA1c）[四分位距 4 与 1 相比=0.74；95%CI，0.62-0.89；趋势 P 值=0.002/FDR=0.04]和丙氨酸氨基转移酶（ALT）[四分位距 4 与 1 相比=0.76；95%CI，0.63-0.91；趋势 P 值=0.002/FDR=0.04]与较低的卵巢癌风险显著相关。按组织学类型分层时，较高的 IGF1 水平与较低的浆液性（四分位距 4 与 1 相比=0.73；95%CI，0.58-0.91；趋势 P 值=0.01/FDR=0.20）和透明细胞癌（四分位距 4 与 1 相比=0.18；95%CI，0.07-0.49；趋势 P 值=0.001/FDR=0.02）风险较低相关，而较高的 HbA1c 水平与较低的浆液性肿瘤风险相关（四分位距 4 与 1 相比=0.73；95%CI，0.59-0.90；趋势 P 值=0.004/FDR=0.08）。
结论
我们观察到循环 IGF1、HbA1c 和丙氨酸氨基转移酶水平升高与卵巢癌风险降低有关。
影响
这些结果表明葡萄糖/氨基酸代谢和胰岛素/IGF1 信号通路可能与卵巢癌的发生有关。需要进一步的研究来复制我们的发现，并阐明代谢系统变化如何影响卵巢癌的发生。
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